TRANSNEURONAL SIGNALS FOR AFFERENT REGULATION

用于传入调节的跨神经元信号

基本信息

批准号：
3461737
负责人：
RICHARD L. HYSON
金额：
$ 10.03万
依托单位：
FLORIDA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-09-01 至 1995-06-30
项目状态：
已结题

项目摘要

Afferent activity has been shown to regulate a number of properties of postsynaptic neurons. It is well known that afferent input regulates the electrical activity of postsynaptic neurons through the action of neurotransmitters. Afferent input, however, also regulates the metabolic activity of postsynaptic neurons, particularly early in development. The signals for this latter form of transneuronal regulation are not known. The brain stem auditory system of the chick has proven to be a useful system for investigation transneuronal regulation of cellular metabolism. Second-order auditory neurons in nucleus magnocellularis (NM, the cochlear nucleus) receive their sole excitatory input from the ipsilateral auditory nerve. Elimination of activity in the auditory nerve on one side of the brain has been shown to alter a number of properties of NM neurons. For example, after a couple of days, a portion of the neurons in NM die and the rest shrink in size. Early after the elimination of auditory nerve activity in young chicks, changes in metabolism in NM neurons have been observed. For example, within 1 hour, there is a dramatic decrease in protein synthesis by NM neurons on the ipsilateral side of the brain. Such changes in NM neurons structure and function, however, are not observed after elimination of auditory nerve activity in adult birds. The proposed experiments investigate the signals involved in the regulation of both the electrical activity and metabolic activity of NM neurons. These experiments will be carried out on both young (1-2 week old) and adult (1 year old) chickens. Regulation of electrical activity is investigated first by analyzing the anatomical distribution of different classes of excitatory amino acid receptors. The physiological effects of excitatory amino acids are then assessed by application of specific agonists and antagonists while recording intracellularly from NM neurons in an in vitro brain slice preparation. Metabolic regulation is investigated by assessing changes in protein synthesis in the in vitro slice preparation after various treatments. Unilateral stimulation of the auditory nerve in vitro has been shown to produce similar changes in protein synthesis as those observed in vivo. Application of specific agonists and antagonists will assess the relative roles of different types of excitatory amino acid receptors and second messenger systems in transneuronal regulation of brain stem auditory system, 2) an understanding of the signals responsible for the regulation of neuronal metabolism in this system and 3) an understanding of age-related differences which may account for the age- dependence in the sensitivity of neurons to alterations of afferent activity.

传入活动已显示用于调节许多特性突触后神经元。众所周知，传入的输入调节突触后神经元的电活动通过神经递质。但是，传入输入也调节代谢突触后神经元的活性，尤其是发育早期。这后一种形式的跨神经元调节的信号尚不清楚。小鸡的脑干听觉系统已被证明是有用的研究细胞代谢的跨神经元调节系统。核细胞核中的二阶听觉神经元（NM，人工耳蜗核）从同侧听到他们的唯一兴奋性输入神经。消除在听觉神经一侧的听觉神经中的活动大脑已被证明会改变NM神经元的许多特性。为了例如，几天后，NM死亡的一部分神经元和休息大小。消除听觉神经后的早期在幼鸡中的活性，NM神经元的代谢变化已经观察到。例如，在1小时内，有很大的下降 NM神经元的蛋白质合成在大脑的同侧。这样的但是，未观察到NM神经元结构和功能的变化消除成年鸟类的听觉神经活动后。提出的实验调查了该调节所涉及的信号 NM神经元的电活动和代谢活性。这些实验将对年轻（1-2周大）和成人（1岁）鸡。电活动的调节是首先通过分析不同的解剖分布进行研究兴奋性氨基酸受体的类别。生理影响的然后，通过应用特异性评估兴奋性氨基酸激动剂和拮抗剂，同时在NM神经元中记录细胞内体外脑切片制剂。研究代谢调节通过评估体外切片制剂中蛋白质合成的变化经过各种治疗。单方面刺激听觉神经体外已被证明会在蛋白质合成中产生类似的变化那些在体内观察到的。特定激动剂和拮抗剂的应用将评估不同类型的兴奋性氨基酸的相对作用大脑跨神经元调节中的受体和第二信使系统 STEM听觉系统，2）对负责信号的理解调节该系统中神经元代谢和3）了解与年龄有关的差异，这可能解释了年龄神经元对传入改变的敏感性的依赖性活动。